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Network based identification of different mechanisms underlying pathogenesis of human papilloma virus‐active and human papilloma virus‐negative oropharyngeal squamous cell carcinoma
Author(s) -
Iman Maryam,
Narimani Zahra,
Hamraz Iman,
Ansari Ebrahim
Publication year - 2018
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.201800072
Subject(s) - phenotype , gene , biology , cancer research , gene expression , papilloma , virus , pathogenesis , cell , immunology , genetics , pathology , medicine
A different molecular mechanism underlying human papilloma virus (HPV)‐negative and HPV‐active pathogenesis is responsible for better response to therapies in HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC). In this study, we aim to provide an insight into molecular basis underlying this distinction and introduce possible targeted therapies for each phenotype. Using weighted gene co‐expression network analysis (WGCNA), our aim was to identify not only differentially expressed genes but also significant coexpressed gene modules responsible for genotype and phenotype distinctions between HPV‐active and HPV‐negative samples. Recognizing differentially expressed genes in each module indicates key regulators that may be ignored in an analysis only based on differential gene expression study. Two modules are investigated in detail in our analysis, related to JAK–STAT dysregulation in HPV‐negative samples, and disruption of cell fate commitment possibly induced by overexpression of BCL2 is observed in the HPV‐active cohort. The existence of differentially expressed oncogenes and potential miRNA role is investigated in our analysis. The other significant module related to keratinization, keratinocyte differentiation, and intermediate filament cytoskeleton organization was discovered in the resulting co‐expression network. A considerable number of genes was downregulated in HPV‐active samples in the relative module, postulating the impairment of cytoskeleton‐related gene expression caused by HPV intervention.